FEATURES

FAMILY

DESCRIPTION

Also known as LEF_BACAN, lef. Lethal factor (LF), which constitutes one of the three proteins composing the anthrax toxin, is able to trigger rapid cell death in macrophages (PubMed:3711080, PubMed:8380282, PubMed:9563949, PubMed:10475971, PubMed:11104681, PubMed:9703991). Acts as a protease that cleaves the N-terminal of most dual specificity mitogen-activated protein kinase kinases (MAPKKs or MAP2Ks) (except for MAP2K5): cleavage invariably occurs within the N-terminal proline-rich region preceding the kinase domain, thus disrupting a sequence involved in directing specific protein-protein interactions necessary for the assembly of signaling complexes (PubMed:9563949, PubMed:10475971, PubMed:11104681, PubMed:9703991, PubMed:14718925). Also cleaves mouse Nlrp1b: host Nlrp1b cleavage promotes ubiquitination and degradation of the N-terminal part of Nlrp1b by the proteasome, thereby releasing the cleaved C-terminal part of Nlrp1b, which polymerizes and forms the Nlrp1b inflammasome followed by host cell pyroptosis (PubMed:10338520, PubMed:19651869, PubMed:31268597, PubMed:30872531). Able to cleave mouse Nlrp1b alleles 1 and 5, while it is not able to cleave Nlrp1b alleles 2, 3 and 4 (PubMed:16429160, PubMed:19651869). In contrast, does not cleave NLRP1 human ortholog (PubMed:19651869). LF is not toxic by itself and only acts as a lethal factor when associated with protective antigen (PA) to form the lethal toxin (LeTx): PA is required for LF translocation into the host cytosol (PubMed:9563949, PubMed:10475971, PubMed:11104681, PubMed:9703991). Interacts (via ATLF domain 1) with the cleaved form of protective antigen (PA-63) anthrax toxin; interaction is required for LF translocation into the host cytoplasm (PubMed:10085027, PubMed:8942659, PubMed:15313199, PubMed:21037566, PubMed:32047164, PubMed:32810181, PubMed:32521227). Interacts with PA-63 homooligomers (either homoheptamers or homooctamers): three molecules of LF bind the PA-63 homoheptamer to form the PA(7)LF(3) complex, in which the relative position of the N-terminal alpha-helices in the three LFs determines which factor is translocated first (PubMed:32810181).

EXTERNAL LINKS

lef

Lethal factor

lef

Molecular Synopsis